This invention relates to certain novel chemical compounds which are useful for treating bacterial infections in mammals, especially humans, and which are new members of the class of antibiotics known as aminoglycoside antibiotics. More particularly, the new compounds of this invention are derivatives of the kanamycins A and B, ribostamycin, xylostasin (the C-3" epimer of ribostamycin), and the neomycins B and C. Said derivatives have an .omega.-amino-2-hydroxyalkyl residue attached to the 1-amino group of the 2-deoxystreptamine moiety, and they possess advantages in use over the corresponding aminoglycoside lacking the said .omega.-amino-2-hydroxyalkyl residue.
Kanamycins A and B, ribostamycin, xylostasin and neomycins B and C are well-known members of the class of antibiotics commonly known as 2-deoxystreptamine aminoglycosides (The Merck Index, An Encyclopedia of Chemicals and Drugs, Eighth Edition, 1968, P. G. Stecher, editor, Merck & Co., Inc., Rahway, N. J., pages 597, 598, 723 and 724; United States Pat. No. 3,661,892; Horii et al., Antimicrobial Agents & Chemotherapy, 5, 578 [1974]). Derivatives of kanamycins A and B with a 4-amino-2-hydroxybutyryl group on the 1-amino group of the 2-deoxystreptamine moiety are disclosed and claimed in U.S. Pat. No. 3,781,268, and analogous 4-amino-2-hydroxybutyryl derivatives of ribostamycin, and xylostasin (the butirosins) are described by Woo et al., Tetrahedron Letters 2625 (1971). Derivatives of aminoglycosides, other than the kanamycins, ribostamycin, xylostasin and the neomycins, with an .omega.-amino-2-hydroxyalkyl group on the 1-amino function, are disclosed in Belgian Pat. No. 818,431 (U.S. Pat. No. 4,002,742).
U.S. Pat. Nos. 3,282,783 and 3,350,387 and British Pat. No. 1,033,394 disclose a broad genus of N-alkylated derivatives of aminoglycoside antibiotics, including derivatives of the kanamycins and neomycins, in which the said N-alkyl groups can contain amino and hydroxy groups. However, these N-alkylated derivatives are reported to be substantially devoid of antibiotic properties by virtue of this alkylation.
U.S. Pat. No. 4,000,261 discloses 1-N-substituted derivatives of 5-epi-kanamycin A and 5-epikanamycin B, in which the 1-N-substituent can be aminohydroxyalkyl. U.S. Pat. No. 4,000,262 discloses 1-N-substituted derivatives of 5-epi-azido-5-deoxy-kanamycins A and B and 5-epi-amino-5-deoxy-kanamycins A and B, in which the 1-N-substituent can be aminohydroxyalkyl. U.S. Pat. No. 4,085,208 discloses 1-N-substituted derivatives of 1-epi-kanamycins A and B, in which the 1-N-substituent can be aminohydroxyalkyl.